1. Field of the Invention
The present invention relates to new application forms of synthetic BPC (Body Protection Compound) peptides comprising 8 to 15 amino acid residues with a molecular weight of 900 to 1,600 daltons, which have organo-protective activity, to processes for their preparation and their use in diagnosis and therapy.
2. Description of the Related Art
Proteins and peptides which are useful for the treatment of various diseases in humans and animals are known. Many of these agents are produced in vivo and may be extracted from animals or humans to prepare pharmaceutical compositions. Examples for pharmaceutically useful proteins or peptides are insulin, erythropoietin, BMPs, interferons, etc. Another example is a gastric juice protein with mucosal protective activity which was recently isolated and named BPC. WO 92/04368 relates to BPC which exhibits body-protective activity and has a molecular weight of about 40,000 daltons, its preparation and its use. WO 93/24521 and WO 94/11394 disclose BPC peptides which have organo-protective activity of the same type as known from the parent protein BPC. Sikiric et al. in: Digestive Diseases and Sciences, 41(1996)7, 1518-1526, describe pentadecapeptide BPC 157, which exhibits when dissolved in water and saline salutary and prophylactic effects on acute pancreatitis and concomitant gastroduodenal lesions in rats.
Thus, the BPC peptides are known for a wide variety of pharmaceutical applications. However, the physicochemical stability of these peptides, for instance in normal saline, is not satisfactory. Furthermore, the application of BPC peptides, in particular by injection of an aqueous solution or in normal saline, causes pain and/or necrosis.
Salts of proteins and peptides are well known in the art. It is for instance known from Bertrand, M. et al. in: Journal of Peptide Research, 49 (1997)3, 269-272, that the effects of particular salts are very selective in respect to the stability and structure of peptides. For instance, the addition of monovalent cations, such as NH.sub.4.sup.+ to a final 0.1 M peptide (poly (Glu-Leu)) solution, induces a transition to a water soluable beta-structure. In contrast, no transition was observed using Li.sup.+, Na.sup.+, or Cs.sup.+ ions.